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Study: Children Should Not Take Antihistamines for Chronic Cough

Side effects outweigh benefits in many cases

April 16, 2008

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Chronic cough can cut into children’s sleep and fray parents’ nerves. Although antihistamines can alleviate cough, possible side effects outweigh their benefits, say authors of a new review of studies from Australia.

“In contrast to recommendations in adults with chronic cough, antihistamines cannot be recommended as empirical therapy for children with chronic cough,” conclude reviewers led by Dr. Anne Chang.

The review adds to the growing body of evidence casting doubt on the use of a variety of medicines for children.

Cough is the most common symptom presented to general practitioners, said Chang, a consultant in pediatric respiratory medicine at the Royal Children’s Hospital in Brisbane and the Menzies School of Health Research in Queensland.

A child is considered to have chronic cough after four weeks. A specific cough is associated with symptoms suggestive of an underlying problem. Nonspecific cough is nonproductive cough -- without gunk -- in the absence of identifiable respiratory disease.

Some children with nonspecific cough have asthma, but most do not.

“Most nonspecific cough is likely post-viral,” said Chang, who has been researching issues related to cough for the past decade. Children with nonspecific cough are treated with a variety of therapies, including antihistamines.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Five studies

The reviewers examined five studies involving about 1,000 children, ranging from six months to 17 years old. Many children had allergies to things like grass, pollen or dust mites, or a family history of allergy.

Two larger studies “described significant improvement” both in children who took antihistamines and those who took placebos “with no significant difference between the two groups,” the authors write.

A smaller study involving 20 school-age children found that cetirizine (Zyrtec) clinically improves cough due to pollen allergy. In that study, the antihistamine was significantly more effective than placebos in reducing chronic cough in children with allergies.

Another study examined the use of ketotifen (Zaditen) to minimize the frequency of asthma attacks in 113 infants ranging from six months to 36 months old. After a four-week no-medication baseline, infants received either a placebo or ketotifen for 16 weeks. Researchers concluded that they were “unable to show a therapeutic advantage of ketotifen over placebo.”

Any effectiveness the drugs have should be weighed against their reported side effects, especially in young children, including “sedation, paradoxical excitability, dizziness, respiratory depression, hallucinations, arrhythmia and death,” Chang writes.

In these studies, however, “most of the events reported were minor, with irritability and gastrointestinal upset being the most common events,” the review says. Four children were withdrawn from one study. A dozen other children felt drowsy after taking medicine.

Chang said that the small study involving Zyrtec reported “no adverse effects.”

Histamine, a compound found in nearly all tissues of the body, plays a role in allergic reactions. It is released in allergic conditions, including asthma, and gives rise to their symptoms. Antihistamine drugs inhibit histamine.

Not equal

Still, all antihistamines are not equal, said Richard Irwin, past president of the American College of Chest Physicians.

The older antihistamines, such as Benadryl, have more anticholinergic activity, which is to say they “dry one out” more, said Irwin, a professor at the University of Massachusetts Medical School.

“These older drugs therefore can work when the cause of the upper airway cough is not due to allergies and they can also work if the cause of the cough is due to allergies,” Irwin said. On the other hand, because the new drugs such as cetirizine [Zyrtec] or loratadine [Claritin] don’t have much anticholinergic activity to speak of, they will only work if the cause of the upper airway cough is due to allergies.”

Newer antihistamines, such as Zyrtec, “have been shown to be of help in children with allergic rhinitis,” Irwin said. “The literature supports using these specific antihistamines when children have cough in association with seasonal allergies that involve the nose.”

Beyond the research, parents continue to seek treatment for their children, spending billions of dollars worldwide on cough and allergy medications every year.

In children, it is important to explain the cause of the cough, Chang said. She recommends that physicians talk to parents about their fears and concerns, and says that parents who smoke should stop. When her own patients show up with a nonspecific cough, Chang uses a cautious, wait-see-and-review approach.

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